Managing the COVID-19 Pandemic: Research Strategies Based on the Evolutionary and Molecular Characteristics of Coronaviruses.
ABSTRACT: Coronavirus disease 2019 (COVID-19), an ongoing global health emergency, is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging in Wuhan, China, in December 2019, it spread widely across the world causing panic-worst ever economic depression is visibly predictable. Coronaviruses (CoVs) have emerged as a major public health concern having caused three zoonotic outbreaks; severe acute respiratory syndrome-CoV (SARS-CoV) in 2002-2003, Middle East respiratory syndrome-CoV (MERS-CoV) in 2012, and currently this devastating COVID-19. Research strategies focused on understanding the evolutionary origin, transmission, and molecular basis of SARS-CoV-2 and its pathogenesis need to be urgently formulated to manage the current and possible future coronaviral outbreaks. Current response to the COVID-19 outbreak has been largely limited to monitoring/containment. Although frantic global efforts for developing safe and effective prophylactic and therapeutic agents are on, no licensed antiviral treatment or vaccine exists till date. In this review, research strategies for coping with COVID-19 based on evolutionary and molecular aspects of coronaviruses have been proposed.
Project description:In December 2019, an acute respiratory disease caused by novel species of coronavirus (SARS-CoV-2), emerged in China and has spread throughout the world. On 11th March 2020, the World Health Organization (WHO) officially declared coronavirus disease 19 (COVID-19) a pandemic, severe coronavirus-mediated human disease. Based on genomic and phylogenetic studies, SARS-CoV-2 might originate from bat coronaviruses and infects humans directly or through intermediate zoonotic hosts. However, the exact origin or the host intermediate remains unknown. Genetically, SARS-CoV-2 is similar to several existing coronaviruses, particularly SARS-CoV, but differs by silent and non-silent mutations. The virus uses different transmission routes and targets cells and tissues with angiotensin-converting enzyme 2 (ACE2) protein, which makes it contagious. COVID-19 shares both the main clinical features and excessive/dysregulated cell responses with the two previous Middle East respiratory syndrome coronavirus (MERS) and severe acute respiratory syndrome coronavirus (SARS) epidemics. In this review, we provide an update of the current knowledge on the COVID-19 pandemic. Gaining a deeper understanding of SARS-CoV-2 structure, transmission routes, and molecular responses, will assist in the prevention and control of COVID-19 outbreaks in the future.
Project description:Since December 2019, the global pandemic caused by the highly infectious novel coronavirus 2019-nCoV (COVID-19) has been rapidly spreading. As of April 2020, the outbreak has spread to over 210 countries, with over 2,400,000 confirmed cases and over 170,000 deaths.1 COVID-19 causes a severe pneumonia characterized by fever, cough and shortness of breath. Similar coronavirus outbreaks have occurred in the past causing severe pneumonia like COVID-19, most recently, severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). However, over time, SARS-CoV and MERS-CoV were shown to cause extrapulmonary signs and symptoms including hepatitis, acute renal failure, encephalitis, myositis and gastroenteritis. Similarly, sporadic reports of COVID-19 related extrapulmonary manifestations emerge. Unfortunately, there is no comprehensive summary of the multiorgan manifestations of COVID-19, making it difficult for clinicians to quickly educate themselves about this highly contagious and deadly pathogen. What is more, is that SARS-CoV and MERS-CoV are the closest humanity has come to combating something similar to COVID-19, however, there exists no comparison between the manifestations of any of these novel coronaviruses. In this review, we summarize the current knowledge of the manifestations of the novel coronaviruses SARS-CoV, MERS-CoV and COVID-19, with a particular focus on the latter, and highlight their differences and similarities.
Project description:With the outbreak of unknown pneumonia in Wuhan, China, in December 2019, a new coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), aroused the attention of the entire world. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19). The World Health Organization declared COVID-19 in China as a Public Health Emergency of International Concern. Two other coronavirus infections-SARS in 2002-2003 and Middle East Respiratory Syndrome (MERS) in 2012-both caused severe respiratory syndrome in humans. All 3 of these emerging infectious diseases leading to a global spread are caused by ?-coronaviruses. Although coronaviruses usually infect the upper or lower respiratory tract, viral shedding in plasma or serum is common. Therefore, there is still a theoretical risk of transmission of coronaviruses through the transfusion of labile blood products. Because more and more asymptomatic infections are being found among COVID-19 cases, considerations of blood safety and coronaviruses have arisen especially in endemic areas. In this review, we detail current evidence and understanding of the transmission of SARS-CoV, MERS-CoV, and SARS-CoV-2 through blood products as of February 10, 2020, and also discuss pathogen inactivation methods on coronaviruses.
Project description:Incidents of viral outbreaks have increased at an alarming rate over the past decades. The most recent human coronavirus known as COVID-19 (SARS-CoV-2) has already spread around the world and shown R0 values from 2.2 to 2.68. However, the ratio between mortality and number of infections seems to be lower in this case in comparison to other human coronaviruses (such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)). These outbreaks have tested the limits of healthcare systems and have posed serious questions about management using conventional therapies and diagnostic tools. In this regard, the use of nanotechnology offers new opportunities for the development of novel strategies in terms of prevention, diagnosis and treatment of COVID-19 and other viral infections. In this review, we discuss the use of nanotechnology for COVID-19 virus management by the development of nano-based materials, such as disinfectants, personal protective equipment, diagnostic systems and nanocarrier systems, for treatments and vaccine development, as well as the challenges and drawbacks that need addressing.
Project description:The 2019 novel coronavirus disease (COVID-19), which is caused by the novel beta coronavirus, SARS-CoV-2, is currently prevalent all over the world, causing thousands of deaths with relatively high virulence. Like two other notable beta coronaviruses, severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 can lead to severe contagious respiratory disease. Due to impaired cellular immunity and physiological changes, pregnant women are susceptible to respiratory disease and are more likely to develop severe pneumonia. Given the prevalence of COVID-19, it is speculated that some pregnant women have already been infected. However, limited data are available for the clinical course and management of COVID-19 in pregnancy. Therefore, we conducted this review to identify strategies for the obstetric management of COVID-19. We compared the clinical course and outcomes of COVID-19, SARS, and MERS in pregnancy and discussed several drugs for the treatment of COVID-19 in pregnancy.
Project description:Following the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), another highly pathogenic coronavirus named SARS-CoV-2 (previously known as 2019-nCoV) emerged in December 2019 in Wuhan, China, and rapidly spreads around the world. This virus shares highly homological sequence with SARS-CoV, and causes acute, highly lethal pneumonia coronavirus disease 2019 (COVID-19) with clinical symptoms similar to those reported for SARS-CoV and MERS-CoV. The most characteristic symptom of patients with COVID-19 is respiratory distress, and most of the patients admitted to the intensive care could not breathe spontaneously. Additionally, some patients with COVID-19 also showed neurologic signs, such as headache, nausea, and vomiting. Increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system inducing neurological diseases. The infection of SARS-CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Furthermore, some coronaviruses have been demonstrated able to spread via a synapse-connected route to the medullary cardiorespiratory center from the mechanoreceptors and chemoreceptors in the lung and lower respiratory airways. Considering the high similarity between SARS-CoV and SARS-CoV2, it remains to make clear whether the potential invasion of SARS-CoV2 is partially responsible for the acute respiratory failure of patients with COVID-19. Awareness of this may have a guiding significance for the prevention and treatment of the SARS-CoV-2-induced respiratory failure.
Project description:More than seven months into the coronavirus disease -19 (COVID-19) pandemic, infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 21.2 million cases and resulted in over 760,000 deaths worldwide so far. As a result, COVID-19 has changed all our lives as we battle to curtail the spread of the infection in the absence of specific therapies against coronaviruses and in anticipation of a proven safe and efficacious vaccine. Common with previous outbreaks of coronavirus infections, SARS and Middle East respiratory syndrome, COVID-19 can lead to acute respiratory distress syndrome (ARDS) that arises due to an imbalanced immune response. While several repurposed antiviral and host-response drugs are under examination as potential treatments, other novel therapeutics are also being explored to alleviate the effects on critically ill patients. The use of mesenchymal stromal cells (MSCs) for COVID-19 has become an attractive avenue down which almost 70 different clinical trial teams have ventured. Successfully trialled for the treatment of other conditions such as multiple sclerosis, osteoarthritis and graft versus host disease, MSCs possess both regenerative and immunomodulatory properties, the latter of which can be harnessed to reduce the severity and longevity of ARDS in patients under intensive care due to SARS-CoV-2 infection.
Project description:Despite to outbreaks of highly pathogenic beta and alpha coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus, the newly emerged 2019 coronavirus (COVID-19) is considered as a lethal zoonotic virus due to its deadly respiratory syndrome and high mortality rate among the human. Globally, more than 3,517,345 cases have been confirmed with 243,401 deaths due to Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19. The antiviral drug discovery activity is required to control the persistence of COVID-19 circulation and the potential of the future emergence of coronavirus. However, the present review aims to highlight the important antiviral approaches, including interferons, ribavirin, mycophenolic acids, ritonavir, lopinavir, inhibitors, and monoclonal antibodies (mAbs) to provoke the nonstructural proteins and deactivate the structural and essential host elements of the virus to control and treat the infection of COVID-19 by inhibiting the viral entry, viral RNA replication and suppressing the viral protein expression. Moreover, the present review investigates the epidemiology, diagnosis, structure, and replication of COVID-19 for better understanding. It is recommended that these proteases, inhibitors, and antibodies could be a good therapeutic option in drug discovery to control the newly emerged coronavirus.HighlightsCOVID-19 has more than 79.5% identical sequence to SARS-CoV and a 96% identical sequence of the whole genome of bat coronaviruses.Acute respiratory distress syndrome (ARDS), renal failure, and septic shock are the possible clinical symptoms associated with COVID-19.Different antivirals, including interferons, ribavirin, lopinavir, and monoclonal antibodies (mAbs) could be the potent therapeutic agents against COVID-19.The initial clinical trials on hydroquinone in combination with azithromycin showed an admirable result in the reduction of COVID-19.The overexpression of inflammation response, cytokine dysregulation, and induction of apoptosis could be an well-organized factors to reduce the pathogenicity of COVID-19.
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.
Project description:The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is one of seven human coronaviruses. G-quadruplexes are intrinsic obstacles to genome replication. Whether G-quadruplexes are present in human coronaviruses is unknown. In the current study, we have predicted that all seven human coronaviruses harbor G-quadruplex sequences. Conserved G-quadruplex sequences in SARS-CoV and SARS-CoV-2 were analyzed and verified by circular dichroism (CD) spectroscopy and Thioflavin T fluorescence assay. Similar to SARS-CoV, SARS-CoV-2 encodes an nsP3 protein, which is predicted to associate with G-quadruplexes. Targeting G-quadruplex sequences in the SARS-CoV-2 genome by G-quadruplex ligands could be a new way to conquer COVID-19.